Fungal infections in patients undergoing bone marrow transplantation: an approach to a rational management protocol

Candida sp. and Aspergillus sp. are the most common fungal pathogens causing infection in bone marrow transplant recipients and represent an increasing cause of morbidity and mortality. At this time there is no generally accepted rule for the antifungal management of these complications. Antifungal drugs in immunocompromised patients are usually administered for prophylaxis, for therapy of specific infections or for empirical or preemptive therapy. The present article reports schedules of administrations and pediatric and adult dosages of the main antifungal drugs presently available, (fluconazole, itraconazole, amphotericin B deoxycholate, lipid formulations of amphotericin B and flucytosine), together with their spectrum of action and main toxicities. Thereafter, the available information about prevention and treatment of fungal infections in bone marrow transplant recipients is summarized. Briefly, fluconazole remains the drug of choice for prevention of Candida infections in bone marrow transplant recipients, while itraconazole has been seldomly used for this indication, due to erratic oral absorption. However, new itraconazole formulations are being studied, that might disclose new clinical perspectives, due to improved bioavailability. The duration of prophylaxis is still an open issue. Resistance to the new azoles may become a problem in the near future. For this reason, it is likely that the approach to the use of these new drugs should be similar to the one commonly used for antibacterial drugs, i.e. based on pathogen-related, drug-related and host-related factors. Mainly due to lack of diagnostic tools, very little studies have been performed for prevention of aspergillosis. Available data seem to show that there might be a role for low-dose intravenous amphotericin B, which has shown to be effective for secondary prophylaxis. Itraconazole and intranasal amphotericin B have been studied, as well. Although fluconazole and itraconazole (in the rare instances in which the oral route is reliable) can also have therapeutic indications, both for empirical and for specific therapy, amphotericin B (with or without flucytosine) remains the main therapeutic option. New antifungal drugs and new supportive strategies (i.e. role of hematopoietic growth factors) are in the research pipeline and will hopefully disclose new perspectives in the near future.